The lethal mutation of the mouse wasted ( wst ) is a deletion that abolishes expression of a tissue-specific isoform of translation elongation factor 1α, encoded by the Eef1a2 gene

Abstract

We have identified the mutation responsible for the autosomal recessive wasted (wst) mutation of the mouse. Wasted mice are characterized by wasting and neurological and immunological abnormalities starting at 21 days after birth; they die by 28 days. A deletion of 15.8 kb in wasted mice abolishes expression of a gene called Eef1a2, encoding a protein that is 92% identical at the amino acid level to the translation elongation factor EF1␣ (locus Eef1a). We have found no evidence for the involvement of another gene in this deletion. Expression of Eef1a2 is reciprocal with that of Eef1a. Expression of Eef1a2 takes over from Eef1a in heart and muscle at precisely the time at which the wasted phenotype becomes manifest. These data suggest that there are tissuespecific forms of the translation elongation apparatus essential for postnatal survival in the mouse.

Immuno-characterization of the switch of peptide elongation factors eEF1A-1/EF-1α and eEF1A-2/S1 in the central nervous system during mouse development

“…Thereafter, eEF1A-1/EF-1α is replaced in the brain, heart, and skeletal muscles by its homologue, eEF1A-2/S1; the reason for this transition, as well as the localization of eEF1A-2/ S1 in different cell populations of the central nervous system (CNS), remain to be characterized. Absence of eEF1A-2/S1 caused by partial deletion of the gene, characterized in spontaneous wasted (wst/wst) mutant mice, is lethal in less than 30 days after birth [2], and is postulated to occur as a result of the absence of elongation factor 1A in brain, heart, and skeletal muscle following the developmental switch [7]. Heterozygous mice (+/wst) do not display any phenotype or abrogated longevity and have a normal pattern of protein expression, similar to wild-type (+/+) animals.…”

Expression of eEF1A2 is associated with clear cell histology in ovarian carcinomas: overexpression of the gene is not dependent on modifications at the EEF1A2 locus

“…The encoded proteins are 92% identical and 98% similar. Whereas lack of eEF1A2 gives rise to the wasted mouse phenotype (Chambers et al, 1998), which involves motor neuron degeneration , inappropriate overexpression has now been linked to cancer. Anand et al (2002) showed that eEF1A2, while not normally expressed in ovary, is expressed in 30% of ovarian tumours .…”

Translational Control in Tumour Progression and Drug Resistance

“…The near-ubiquitous form, eEF1A1, is expressed in all tissues throughout development but is absent in adult muscle and heart expressing eEF1A2 instead [58,59]. eEF1A2 is also found in some other cell types including large motor neurons, islet cells in the pancreas and enteroendocrine cells in the gut [60,61]. Despite sharing 92% sequence identity, paralogous human eEF1A1 and eEF1A2 have different functional profiles.…”